Activation of macrophages for tumor cell cytotoxicity: identification of indomethacin sensitive and insensitive pathways.
Macrophages can be activated for tumor cell cytotoxicity by endotoxin- or lymphokine-containing solutions, and in both cases activation can be blocked by the addition of indomethacin. In contrast, the activation of macrophages by nonadherent or inflammatory peritoneal cells or antibody-coated tumor cells is not affected by indomethacin. These results demonstrate that there are at least 2 distinct pathways of macrophage activation, only 1 of which is affected by the addition of the drug. Activation by endotoxin that is indomethacin sensitive requires 2 steps. At present, the first is undefined and not blocked by indomethacin, but the second is inhibited by the drug and appears to require the production of E series prostaglandins. Our results also suggest that neither step alone is sufficient to activate macrophages for cytotoxicity.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000494:pharmacology
D008070:Lipopolysaccharides; D008222:Lymphokines; D011458:Prostaglandins E; D001241:Aspirin; D007213:Indomethacin